Researchers from Michigan State University and the Czech Academy of Sciences have discovered a method to recreate powerful compounds from wolfsbane and larkspur in the laboratory, according to a Jul. 31 announcement. These plants are known for their neurotoxicity and potential to cause paralysis in small doses, but they also possess properties that counter pain, malaria, cancer, and pests.
The collaborative research is published in the journal Molecular Plant. Garret Miller, co-first author of the paper and assistant professor of biotechnology at University of Michigan-Flint, said, "These plants have been used in different forms of medicine throughout the world for thousands of years." Miller added, "We know they interreact with our bodies in so many ways, and understanding how to create them can help provide totally new routes of testing."
Björn Hamberger, study author and James K. Billman Endowed Professor at MSU's Department of Biochemistry and Molecular Biology, said that plants are highly effective chemists due to millions of years upgrading their arsenal of natural compounds for survival. Lana Mutabdžija, a graduate student at the Czech Academy of Sciences and co-first author on the paper, said humans use many plant-derived molecules daily: "These include caffeine, capsaicin, menthol and vanillin... many medicines we use today either come directly from plants or are inspired by plant chemistry."
The team focused on diterpenoid alkaloids—complex chemicals produced by larkspur (delphinium) and wolfsbane (monkshood). Despite being isolated nearly 200 years ago, some such as aconitine have not yet been synthesized successfully in laboratories. The project advanced when Hamberger met Tomáš Pluskal’s group from the Czech Academy during a conference; both teams were pursuing similar research on these alkaloids.
To identify how these plants produce diterpenoid alkaloids like atisinium, researchers tracked thousands of genes across multiple species to find which were active during compound production. Miller compared this process to an assembly line: "If you have ten steps...and suddenly one quits, the next steps can't happen." After identifying promising genes from wolfsbane and larkspur, they inserted them into tobacco plants which then produced atisinium via six unique enzymes.
Hamberger said knowing these biochemical steps provides a foothold towards unlocking more medicinal qualities within this chemical family: "Our vision is to provide green, sustainable tools that will allow us harness these plants' natural power."
